Search

Replacement of the exocrine parenchyma by fibrous tissue is a main characteristic of chronic pancreatitis. Understanding the mechanisms of pancreatic fibrogenesis is critical for the development of preventive and therapeutic interventions. Cyclooxygenase-2 (COX-2), a rate-limiting enzyme for prostaglandin synthesis, is expressed in patients with chronic pancreatitis. However, it is unknown whether COX-2 can cause chronic pancreatitis. To investigate the roles of pancreatic acinar COX-2 in fibrogenesis and the development of chronic pancreatitis, COX-2 was ectopically expressed specifically in pancreatic acinar cells in transgenic mice. Histopathological changes and expression levels of several profibrogenic factors related to chronic pancreatitis were evaluated. COX-2 was expressed in the pancreas of the transgenic mice, as detected by Western blot analysis. Immunohistochemical staining showed COX-2 was specifically expressed in pancreatic acinar cells. COX-2 expression led to progressive changes in the pancreas, including pancreas megaly, persistent inflammation, collagen deposition, and acinar-to-ductal metaplasia. Quantitative RT-PCR and immunostaining showed that profibrogenic factors were upregulated and pancreatic stellate cells were activated in the COX-2 transgenic mice. Expression of COX-2 in pancreatic acinar cells is sufficient to induce chronic pancreatitis. Targeting this pathway may be valuable in the prevention of chronic pancreatitis. [ABSTRACT FROM AUTHOR]

Background/Aims: Neuropathy target esterase (NTE, also known as neurotoxic esterase) is proven to deacylate phosphatidylcholine (PC) to glycerophosphocholine as a phospholipase B. Recently; studies showed that artificial phosphatidylserine/PC microvesicles can induce preeclampsia (PE)-like changes in pregnant mice. However, it is unclear whether NTE plays a key role in the pathology of PE, a pregnancy-related disease, which was characterized by deficient trophoblast invasion and reduced trophoblast-mediated remodeling of spiral arteries. The aim of this study was to investigate the expression pattern of NTE in the placenta from women with PE and normal pregnancy, and the molecular mechanism of NTE involved in the development of PE. Methods: NTE expression levels in placentas from 20 pregnant women with PE and 20 healthy pregnant women were detected using quantitative PCR and immunohistochemistry staining. The effect of NTE on trophoblast migration and invasion and the underlying mechanisms were examined in HTR-8/SVneo cell lines by transfection method. Results: NTE mRNA and protein expression levels were significantly decreased in preeclamptic placentas than normal control. Over-expression of NTE in HTR-8/SVneo cells significantly promoted trophoblast cells migration and invasion and was associated with increased MMP-9 levels. Conversely, shRNA-mediated down-regulation of NTE markedly inhibited the cell migration and invasion. In addition, silencing NTE reduced the MMP-9 activity and phosphorylated Erk1/2 and AKT levels. Conclusions: Our results suggest that the decreased NTE may contribute to the development of PE through impairing trophoblast invasion by down-regulating MMP-9 via the Erk1/2 and AKT signaling pathway. [ABSTRACT FROM AUTHOR]

Surface properties of nanoceria can strongly affect the catalytic performance in oxidation reactions. In this work, a simple but efficient post-treatment, where H2O2 is used as a complexing agent to dissolve Ce3+ from the surface of CeO2 nanorods with the help of ultrasonic treatment, is carried out to tune the surface properties and increase their catalytic performance for catalytic wet air oxidation (CWAO) of phenol. It is found that the dissolution of Ce3+ from the surface of CeO2 nanorods can create more surface defects and result in a much rougher surface. The H2O2--ultrasonic treatment can also increase Ce3+ concentration, create more surface oxygen vacancies, and narrow the band gap of CeO2 nanorods. These properties enable H2O2--ultrasonic-treated CeO2 nanorods (CeO2-H2O2-sf) to possess strong oxidizing ability to effectively oxidize phenol. Additionally, for the sake of comparison, other post-treatments, including calcination, H2O2, and ultrasonic--H2O, are also imposed on CeO2 nanorods. [ABSTRACT FROM AUTHOR]

Surface properties of nanoceria can strongly affect the catalytic performance in oxidation reactions. In this work, a simple but efficient post-treatment, where H2O2 is used as a complexing agent to dissolve Ce3+ from the surface of CeO2 nanorods with the help of ultrasonic treatment, is carried out to tune the surface properties and increase their catalytic performance for catalytic wet air oxidation (CWAO) of phenol. It is found that the dissolution of Ce3+ from the surface of CeO2nanorods can create more surface defects and result in a much rougher surface. The H2O2-ultrasonic treatment can also increase Ce3+ concentration, create more surface oxygen vacancies, and narrow the band gap of CeO2 nanorods. These properties enable H2O2-ultrasonic-treated CeO2 nanorods (CeO2-H2O2-sf) to possess strong oxidizing ability to effectively oxidize phenol. Additionally, for the sake of comparison, other post-treatments, including calcination, H2O2, and ultrasonic-H2O, are also imposed on CeO2 nanorods. [ABSTRACT FROM AUTHOR]

Currently, an effective targeted therapy for pancreatitis is lacking. Hereditary pancreatitis (HP) is a heritable, autosomal-dominant disorder with recurrent acute pancreatitis (AP) progressing to chronic pancreatitis (CP) and a markedly increased risk of pancreatic cancer. In 1996, mutations in PRSS1 were linked to the development of HP. Here, we developed a mouse model by inserting a full-length human PRSS1R122H gene, the most commonly mutated gene in human HP, into mice. Expression of PRSS1R122H protein in the pancreas markedly increased stress signaling pathways and exacerbated AP. After the attack of AP, all PRSS1R122H mice had disease progression to CP, with similar histologic features as those observed in human HP. By comparing PRSS1R122H mice with PRSS1WT mice, as well as enzymatically inactivated Dead-PRSS1R122H mice, we unraveled that increased trypsin activity is the mechanism for R122H mutation to sensitize mice to the development of pancreatitis. We further discovered that trypsin inhibition, in combination with anticoagulation therapy, synergistically prevented progression to CP in PRSS1R122H mice. These animal models help us better understand the complex nature of this disease and provide powerful tools for developing and testing novel therapeutics for human pancreatitis. [ABSTRACT FROM AUTHOR]

Currently, an effective targeted therapy for pancreatitis is lacking. Hereditary pancreatitis (HP) is a heritable, autosomaldominant disorder with recurrent acute pancreatitis (AP) progressing to chronic pancreatitis (CP) and amarkedly increased risk of pancreatic cancer. In 1996, mutations in PRSS1 were linked to the development of HP. Here, we developed a mouse model by inserting a full-length human PRSS1R122H gene, the most commonly mutated gene in human HP, into mice. Expression of PRSS1R122H protein in the pancreas markedly increased stress signaling pathways and exacerbated AP. After the attack of AP, all PRSS1R122H mice had disease progression to CP, with similar histologic features as those observed in human HP. By comparing PRSS1R122H mice with PRSS1WT mice, as well as enzymatically inactivated Dead-PRSS1R122H mice, we unraveled that increased trypsin activity is the mechanism for R122H mutation to sensitize mice to the development of pancreatitis. We further discovered that trypsin inhibition, in combination with anticoagulation therapy, synergistically prevented progression to CP in PRSS1R122H mice. These animal models help us better understand the complex nature of this disease and provide powerful tools for developing and testing novel therapeutics for human pancreatitis. [ABSTRACT FROM AUTHOR]

N-type polycrystalline skutterudite compounds Ni0:15Co3:85Sb12 and Fe0:2Ni0:15Co3:65Sb12 with the bcc crystal structure were synthesized by high pressure and high temperature (HPHT) method. The synthesis time was sharply reduced to approximately half an hour. Typical microstructures connected with lattice deformations and dislocations were incorporated in the samples of Ni0:15Co3:85Sb12 and Fe0:2Ni0:15Co3:65Sb12 after HPHT. Electrical and thermal transport properties were meticulously researched in the temperature range of 300 K to 700 K. The Fe0:2Ni0:15Co3:65Sb12 sample shows a lower thermal conductivity than that of Ni0:15Co3:85Sb12. The dimensionless thermoelectric figure-of-merit (zT) reaches the maximal values of 0.52 and 0.35 at 600 K and 700 K respectively, for Ni0:15Co3:85Sb12 and Fe0:2Ni0:15Co3:65Sb12 samples synthesized at 1 GPa. [ABSTRACT FROM AUTHOR]

Background: As a plasticizer, plastic softener, and flame-retardant, tri-ortho-cresyl phosphate (TOCP) is and has been widely used in industry and reported to have a toxic effect on the male reproductive system in animals besides neurotoxicity and immunotoxicity. We have reported that TOCP inhibits spermatogenesis and induces autophagy of rat spermatogonial stem cells, but it is still unknown whether TOCP induces autophagy of mouse Leydig cells and its potential mechanism. Methods: Cell viability was observed by MTT assay. Level of testosterone was measured by radioimmunoassay. Apoptosis was observed by AnnexinV-FITC/PI assay. The contents of LC3, Atg5-Atg12, and Beclin 1 were detected by Western blotting analysis. Autophagosomes were investigated by transmission electron microscopy. The contents of MDA and GSH and the activities of SOD, GSH-PX, total antioxidant status (TAS) and total oxidant status (TOS) were measured by oxidative stress kits. Results: The present study shows that TOCP markedly inhibited viability and testosterone output of mouse Leydig TM3 cells but had no effect on apoptosis. However, TOCP significantly increased both LC3-II and the ratio of LC3-II to LC3-I and the contents of autophagy proteins Atg5 and Beclin 1. Transmission electron microscopy (TEM) showed that TOCP increased autophagic vacuoles of the cytoplasm, indicating that TOCP could induce autophagy of the cells. TOCP significantly induced oxidative stress of mouse Leydig TM3 cells. H2O2 also inhibited viability and induced autophagy of the cells; however, inhibition of oxidative stress by N-acetyl-L-cysteine (NAC) could rescue the inhibition of cell viability and induction of autophagy by TOCP. Conclusions: The results show oxidative stress might be involved in TOCP-induced autophagy of mouse Leydig TM3 cells. [ABSTRACT FROM AUTHOR]